Cone Dystrophy

NORD gratefully acknowledges John Heckenlively, MD, Professor of Ophthalmology and Visual Sciences, University of Michigan, for assistance in the preparation of this report.

Synonyms of Cone Dystrophy

retinal cone degeneration

retinal cone dystrophy

Subdivisions of Cone Dystrophy

progressive cone dystrophy

stationary cone dystrophy

General Discussion

Cone dystrophy is a general term used to describe a group of rare eye disorders that affect the cone cells of the retina. Cone dystrophy can variably cause a variety of symptoms including decreased visual clarity (acuity) when looking straight ahead (central vision), a reduced ability to see colors and an increased sensitivity to light (photophobia). Cone dystrophy may be broken down into two broad groups - stationary and progressive. In stationary cone dystrophy symptoms tend to remain stable and are usually present at birth or early childhood. In progressive cone dystrophy symptoms slowly become worse over time. There are several different forms of cone dystrophy. The age of onset, progression and severity of cone dystrophy can vary greatly from one person to another, even among individuals with the same type of cone dystrophy. Some forms of cone dystrophy are inherited; other forms appear to occur spontaneously for no apparent reason (sporadically).

A variety of different and confusing names have been used to describe the various forms of cone dystrophy. Some researchers limit the term "cone dystrophy" to the progressive forms of the disorder. Other researchers use cone dystrophy as an umbrella term for both the stationary and progressive forms of cone dystrophy - examples of which include achromatopsia, incomplete achromatopsia, blue cone monochromatism, and X-linked progressive cone dystrophy. This report is a general overview report on stationary and progressive cone dystrophy. For more information on an individual form of cone dystrophy use the disorder's specific name as your search term in the Rare Disease Database or contact one of the organizations listed in the resources section of this report.

Signs & Symptoms

The symptoms of cone dystrophy may vary from one person to another, even among individuals with the same form of the disorder. The age of onset, specific symptoms, severity, and progression (if any) can vary greatly. The amount of vision loss varies and is difficult to predict. Affected individuals should talk to their physician and medical team about their specific case and associated symptoms.

Cone dystrophy results from damage to the cone cells of the retinas. The retinas are the thin layers of nerve cells that line that inner surface of the back of the eyes. The retinas sense light and convert it to nerve signals, which are then relayed to the brain through the optic nerve. The retina has two main types of cells – cones and rods. Cone and rod cells are called photoreceptors because they detect and respond to light stimulus.

Cone cells are found throughout the retina with the highest concentration clustered in the oval-shaped, yellowish area near the center of the retina (macula). Cone cells are involved in the part of vision that enables a person to see fine details, read or recognize faces. Cone cells also play a role in the perception of color. Cone cells function best in bright light. Rod cells are found throughout the retina with the exception of the center. Rod cells enable people to see in low or limited light.

Cone dystrophy is sometimes broken down into two broad groups – stationary and progressive. Stationary cone dystrophy is usually present during infancy or early childhood, and symptoms usually remain the same throughout life. In progressive cone dystrophy, associated symptoms become worse over time. The rate of progression and age of onset, however, can vary greatly from one person to another. Progressive cone dystrophy usually develops in late childhood or early during adulthood.

Damage to cone cells can result in decreased clarity of vision (reduced visual acuity) when looking straight ahead (central vision), a reduced ability to see colors and an abnormal sensitivity to light (photophobia). In some cases, affected individuals may not be able to see color at all. Some affected individuals may develop rapid, involuntary eye movements (nystagmus).

In the progressive form of cone dystrophy, vision continues to deteriorate over time. In many cases vision may deteriorate so that a person is considered “legally” blind (i.e., vision that is 20/200 or worse). Complete blindness is uncommon in individuals with cone dystrophy. Side (peripheral) vision is usually unaffected as well. Individuals with cone dystrophy can usually see well at night or in low light situations because the rod cells are usually unaffected.

In rare cases, late in the disease course, some rod cells may become involved.

Causes

Many cases of cone dystrophy occur randomly for no identifiable reason (sporadically). Some forms are inherited as an autosomal dominant, autosomal recessive or X-linked recessive trait. Inherited forms of cone dystrophy are due to mutations to one of several different genes that have been linked to cone dystrophy. These genes contain instructions for making certain proteins, specifically proteins that play vital roles in the development, function or overall health of cone cells. The exact, underlying mechanisms that cause cone dystrophy are not fully understood.

Mutated genes in cone dystrophy can be inherited as an autosomal dominant, autosomal recessive or X-linked recessive trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25 percent chance with each pregnancy to have a carrier daughter like themselves, a 25 percent chance to have a non-carrier daughter, a 25 percent chance to have a son affected with the disease, and a 25 percent chance to have an unaffected son.

Less often, cone dystrophy may be inherited as an autosomal recessive trait. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.

Affected Populations

Cone dystrophy affects males and females in equal numbers when it occurs sporadically or is inherited as an autosomal dominant or recessive trait. The X-linked recessive form of cone dystrophy only affects males fully, although some females may have mild symptoms of the disorder. The exact incidence of cone dystrophy is unknown and estimates tend to vary in the medical literature. Most sources estimate the incidence as approximately 1 in 30,000 individuals in the general population. Cone dystrophy is usually present in early infancy or during childhood or early adulthood. However, the disorder has been reported to develop in individuals of all ages including older adults.

Related Disorders

Symptoms of the following disorders can be similar to those of cone dystrophy. Comparisons may be useful for a differential diagnosis.

Cone-rod dystrophies are a rare group of eye disorders that affect both the cone and rod cells of the retina. In some cases, individuals experience deterioration of the cone cells more severely than the rod cells. In these cases, the initial symptoms are decreased clarity (acuity) of vision when looking straight ahead (central), loss of the ability to perceive color and an abnormal sensitivity to light (photophobia). When the rod cells become more involved, affected individuals experience a decreased ability to see at night or in low light situations and may lose the ability to see clearly to the sides (peripheral vision). In rare cases, cone and rod cells deteriorate simultaneously and these symptoms occur at approximately the same time. Most cases of cone-rod dystrophies occur due to mutations of certain genes. Several different genes have been linked to cone-rod dystrophy. Cone-rod dystrophies can be inherited as autosomal recessive, dominant, X-linked or mitochondrial (maternally-inherited) traits.

Leber’s congenital amaurosis (LCA) is a rare genetic eye disorder where many different genes have been found to be involved. Affected infants are often blind at birth or lose their sight within the first few of years of life. Other symptoms may include crossed eyes (strabismus); rapid, involuntary eye movements (nystagmus); unusual sensitivity to light (photophobia); clouding of the lenses of the eyes (cataracts); and/or abnormal protrusion of the front (anterior), clear portion of the eye through which light passes (cornea) (keratoconus). In addition, some infants with complicated syndromes from other genes may exhibit hearing loss, mental retardation, and/or a delay in the acquisition of skills that require the coordination of mental and muscular activity (psychomotor retardation). Leber’s congenital amaurosis is usually inherited as an autosomal recessive trait. (For more information on this disorder, choose “Leber’s Congenital Amaurosis” as your search term in the Rare Disease Database.)

Stargardt disease is a rare juvenile form of macular degeneration. Macular degeneration is a general term for a group of eyes disorders characterized by the deterioration of the oval-shaped yellow spot (macula) near the center of the retina. The macula is essential for proper vision when looking straight ahead (central vision) and with seeing fine details. Stargardt disease may cause symptoms during childhood or symptoms may not become apparent until the 30s or 40s. Central vision is usually affected in most cases and affected individuals may have trouble reading or have spots in their field of vision. Later in the course of the disease, the ability to perceive color is affected. Affected individuals may also need more time than normal to adjust from going to a bright environment or a dark one. Peripheral vision and the ability to see at night or in low light situations are usually unaffected. Stargardt disease is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Stargardt” as your search term in the Rare Disease Database.)

Syndromic cone dystrophy is a general term for cone dystrophy when it occurs as part of a larger syndrome. These syndromes include Bardet-Biedl syndrome, Refsum disease, Batten disease, NARP syndrome and spinocerebellar ataxia type 7. These disorders have additional symptoms unrelated to cone dystrophy. (For more information on this disorder, choose the specific disorder name as your search term in the Rare Disease Database.)

Diagnosis

A diagnosis of cone dystrophy is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and the diagnostic test is a standardized electroretinogram. Normal ophthalmological exams that measure visual acuity, the ability to perceive color and a person's field of vision are used to help obtain a diagnosis.

During an ERG, eye drops are used to numb the eye before placing a special contact lens-electrode on the eye. The patient then watches a set of flashing lights in order to stimulate the retina. Doctors can then measure the electrical signals made by the cone and rod cells. A weak or absent signal of cone cells indicates cone dystrophy. An ERG test is performed twice – once in a bright room and once in a dark room. The test can determine whether cone and rod cells are functioning properly.

Standard Therapies

Treatment

There is no cure for cone dystrophy. Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may include using tinted lenses or dark sunglass in bright environments and magnifying devices to assist in reading and other similar activities.

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

Years Published

1991, 1999, 2007, 2010

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